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Febuxostat

PubChem CID
134018
Structure
Febuxostat_small.png
Febuxostat_3D_Structure.png
Febuxostat__Crystal_Structure.png
Molecular Formula
Synonyms
  • Febuxostat
  • 144060-53-7
  • Adenuric
  • Uloric
  • 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylic acid
Molecular Weight
316.4 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-18
Description
Febuxostat is a 1,3-thiazolemonocarboxylic acid that is 4-methyl-1,3-thiazole-5-carboxylic acid which is substituted by a 3-cyano-4-(2-methylpropoxy)phenyl group at position 2. It is an orally-active, potent, and selective xanthine oxidase inhibitor used for the treatment of chronic hyperuricaemia in patients with gout. It has a role as an EC 1.17.3.2 (xanthine oxidase) inhibitor. It is an aromatic ether, a nitrile and a 1,3-thiazolemonocarboxylic acid.
Febuxostat is a non-purine xanthine oxidase (XO) inhibitor. In early 2008, febuxostat was granted marketing authorization by the European Commission for the treatment of chronic hyperuricemia and gout. In the following year, the FDA for approved febuxostat for use in the chronic management of hyperuricemia in adult patients with gout who have an inadequate response or intolerance to [allopurinol]. Gout is a form of arthritis that is caused by the accumulation of uric acid crystal in or around a joint, leading to inflammation and further deposition of uric acid crystal deposition in bones, joints, tissues, and other organs in the long term. Gout is closely associated with hyperuricemia. Febuxostat works by inhibiting the activity of an enzyme that is responsible for the synthesis of uric acid, thereby reducing serum uric acid levels. In February 2019, a black box warning for febuxostat was added, based on the findings of a post-market clinical study (the CARES trial) where there was an increased risk of cardiovascular (CV) fatal outcomes in patients with gout and known cardiovascular disease treated with febuxostat, when compared to those treated with allopurinol. The manufacturer and the FDA advise health professionals to limit the use of febuxostat to second-line therapy in patients who have inadequate response or intolerance to allopurinol, and to avoid the use of febuxostat in patients with cardiovascular diseases.
Febuxostat is a Xanthine Oxidase Inhibitor. The mechanism of action of febuxostat is as a Xanthine Oxidase Inhibitor.
See also: Febuxostat hemihydrate (is active moiety of).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Febuxostat.png

1.2 3D Conformer

1.3 Crystal Structures

1 of 3
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CCDC Number
Associated Article
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C16H16N2O3S/c1-9(2)8-21-13-5-4-11(6-12(13)7-17)15-18-10(3)14(22-15)16(19)20/h4-6,9H,8H2,1-3H3,(H,19,20)
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

BQSJTQLCZDPROO-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC1=C(SC(=N1)C2=CC(=C(C=C2)OCC(C)C)C#N)C(=O)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C16H16N2O3S
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEBI ID

2.3.5 ChEMBL ID

2.3.6 DrugBank ID

2.3.7 DSSTox Substance ID

2.3.8 HMDB ID

2.3.9 KEGG ID

2.3.10 Metabolomics Workbench ID

2.3.11 NCI Thesaurus Code

2.3.12 Nikkaji Number

2.3.13 NSC Number

2.3.14 PharmGKB ID

2.3.15 Pharos Ligand ID

2.3.16 RXCUI

2.3.17 Wikidata

2.3.18 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid
  • 6720, TEI
  • febuxostat
  • TEI 6720
  • TEI-6720
  • TEI6720
  • uloric

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
316.4 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
3.9
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
6
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
316.08816355 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
316.08816355 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
111 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
22
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
448
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Melting Point

238-239°
Patent WO2012056442 A1

3.2.2 Solubility

<1 mg/mL
Selleck Chemicals Safety Data Sheet

3.2.3 Collision Cross Section

180.6 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

158.34 Ų [M+H-H2O]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

202.43 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

179.28 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

171.19 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
Pharmaceuticals -> unsed in Switzerland 2014-2016
S113 | SWISSPHARMA24 | 2024 Swiss Pharmaceutical List with Metabolites | DOI:10.5281/zenodo.10501043
3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Antigout Agents; Gout Suppressants
Human drug -> Prescription; None (Tentative Approval); Discontinued; Active ingredient (FEBUXOSTAT)
Human drug -> Prescription
Human drugs -> Antigout preparations -> Human pharmacotherapeutic group -> EMA Drug Category
Paediatric drug

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 MS-MS

1 of 2
Spectra ID
Instrument Type
LC-ESI-qTof
Ionization Mode
Positive
Top 5 Peaks

261.033844 51304

317.095581 22164

217.043015 8176

262.035309 7636

318.097412 2508

Thumbnail
Thumbnail
Notes
From GNPS Library
2 of 2
Spectra ID
Ionization Mode
positive
Top 5 Peaks

261.033844 100

317.095581 43.20

217.043015 15.94

262.035309 14.88

318.097412 4.89

Thumbnail
Thumbnail
Notes
instrument=qTof

4.1.2 LC-MS

1 of 19
View All
Authors
F. Jud [dtc], K. Arturi [dtc], J. Hollender [dtc], A. Dax [com]
Instrument
Q Exactive Plus
Instrument Type
LC-ESI-QFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
15 % (nominal)
Fragmentation Mode
HCD
Column Name
XBridge C18 3.5um, 2.1x50mm, Waters
Retention Time
11.644 min
Precursor m/z
317.0954
Precursor Adduct
[M+H]+
Top 5 Peaks

317.0954 999

261.0326 395

Thumbnail
Thumbnail
License
CC BY-SA
2 of 19
View All
Authors
F. Jud [dtc], K. Arturi [dtc], J. Hollender [dtc], A. Dax [com]
Instrument
Q Exactive Plus
Instrument Type
LC-ESI-QFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
30 % (nominal)
Fragmentation Mode
HCD
Column Name
XBridge C18 3.5um, 2.1x50mm, Waters
Retention Time
11.644 min
Precursor m/z
317.0954
Precursor Adduct
[M+H]+
Top 5 Peaks

261.0326 999

317.0954 43

Thumbnail
Thumbnail
License
CC BY-SA

4.1.3 Other MS

1 of 3
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Authors
EPA CCTE and Agilent Technologies
Instrument Type
ESI-QTOF
MS Level
MS2
Ionization Mode
NEGATIVE
Ionization
ESI
Collision Energy
20
Precursor m/z
315.0808867
Precursor Adduct
[M-H]-
Top 5 Peaks

70.996094 999

71.025086 38

271.091057 22

71.041033 22

Thumbnail
Thumbnail
License
CC BY
2 of 3
View All
Authors
EPA CCTE and Agilent Technologies
Instrument Type
ESI-QTOF
MS Level
MS2
Ionization Mode
NEGATIVE
Ionization
ESI
Collision Energy
10
Precursor m/z
315.0808867
Precursor Adduct
[M-H]-
Top 5 Peaks

271.091057 999

70.996094 680

71.025086 20

71.041033 12

Thumbnail
Thumbnail
License
CC BY

4.2 IR Spectra

4.2.1 FTIR Spectra

Instrument Name
Bio-Rad FTS
Technique
KBr0
Source of Spectrum
Forensic Spectral Research
Source of Sample
Cayman Chemical Company
Catalog Number
<a href=https://www.caymanchem.com/product/14127>14127</a>
Lot Number
0446547-22
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Febuxostat is indicated for the chronic management of hyperuricemia in adult patients with gout who have an inadequate response to a maximally titrated dose of [allopurinol], who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable. It is not recommended for the treatment of asymptomatic hyperuricemia or secondary hyperuricemia.
Febuxostat Mylan is indicated for the prevention and treatment of hyperuricaemia in adult patients undergoing chemotherapy for haematologic malignancies at intermediate to high risk of Tumor Lysis Syndrome (TLS). Febuxostat Mylan is indicated for the treatment of chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history, or presence of, tophus and/or gouty arthritis ). Febuxostat Mylan is indicated in adults.

7.2 LiverTox Summary

Febuxostat is a newly introduced nonpurine xanthine oxidase inhibitor used for the treatment of gout. Chronic febuxostat therapy has been associated with minor serum aminotransferase elevations, but has yet to be linked to cases of clinically apparent acute liver injury.

7.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Antigout Agents; Gout Suppressants
Antigout Agents/Gout Suppressants

7.4 FDA Medication Guides

Drug
Active Ingredient
FEBUXOSTAT
Form;Route
TABLET;ORAL
Company
TAKEDA PHARMS USA
Date
4/17/23

7.5 FDA Approved Drugs

7.6 FDA Orange Book

7.7 FDA National Drug Code Directory

7.8 Drug Labels

Drug and label
Active ingredient and drug

7.9 Clinical Trials

7.9.1 ClinicalTrials.gov

7.9.2 EU Clinical Trials Register

7.9.3 NIPH Clinical Trials Search of Japan

7.10 EMA Drug Information

1 of 4
View All
Category
Human drugs
Therapeutic area
Hyperuricemia; Arthritis, Gouty; Gout
Active Substance
febuxostat
INN/Common name
febuxostat
Pharmacotherapeutic Classes
Antigout preparations
Status
This medicine is authorized for use in the European Union
Company
Mylan Pharmaceuticals Limited
Market Date
2017-06-15
2 of 4
View All
Category
Human drugs
Therapeutic area
Hyperuricemia; Gout
Active Substance
febuxostat
INN/Common name
febuxostat
Pharmacotherapeutic Classes
Antigout preparations
Status
This medicine is authorized for use in the European Union
Company
Krka, d.d., Novo mesto
Market Date
2019-03-28

7.11 Japan PMDA Drugs

1 of 2
Brand Name
Feburic
Non-proprietary Name
Febuxostat
Approval Note
Initial Approval
Approval Date
January 2011
Review Document
2 of 2
Brand Name
Feburic
Non-proprietary Name
Febuxostat
Approval Note
Partial Change Approval
Approval Date
May 2016
Review Document

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Febuxostat is a novel, selective xanthine oxidase/dehydrogenase inhibitor that works by decreasing serum uric acid in a dose-dependent manner. In healthy subjects, febuxostat decreased the mean serum uric acid and serum xanthine concentrations, as well as the total urinary uric acid excretion. Febuxostat at daily doses of 40-80 mg reduced the 24-hour mean serum uric acid concentrations by 40 to 55%. Closely related to the drug-induced reduction of serum uric acid levels and mobilization of urate crystals in tissue deposits, febuxostat is associated with gout flares. Unlike [allopurinol] and [oxypurinol], febuxostat has no inhibitory actions against other enzymes involved in purine and pyrimidine synthesis and metabolism, because it does not structurally resemble purines or pyrimidines.

8.2 MeSH Pharmacological Classification

Gout Suppressants
Agents that increase uric acid excretion by the kidney (URICOSURIC AGENTS), decrease uric acid production (antihyperuricemics), or alleviate the pain and inflammation of acute attacks of gout. (See all compounds classified as Gout Suppressants.)

8.3 FDA Pharmacological Classification

1 of 2
FDA UNII
101V0R1N2E
Active Moiety
FEBUXOSTAT
Pharmacological Classes
Established Pharmacologic Class [EPC] - Xanthine Oxidase Inhibitor
Pharmacological Classes
Mechanisms of Action [MoA] - Xanthine Oxidase Inhibitors
FDA Pharmacology Summary
Febuxostat is a Xanthine Oxidase Inhibitor. The mechanism of action of febuxostat is as a Xanthine Oxidase Inhibitor.
2 of 2
Non-Proprietary Name
FEBUXOSTAT
Pharmacological Classes
Xanthine Oxidase Inhibitor [EPC]; Xanthine Oxidase Inhibitors [MoA]

8.4 ATC Code

M04AA03
S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

M - Musculo-skeletal system

M04 - Antigout preparations

M04A - Antigout preparations

M04AA - Preparations inhibiting uric acid production

M04AA03 - Febuxostat

8.5 Absorption, Distribution and Excretion

Absorption
After oral administration, about 85% of febuxostat is absorbed rapidly. Tmax ranges from 1 to 1.5 hours. Following once-daily oral administration, Cmax was approximately 1.6 ± 0.6 mcg/mL at a dose of 40 mg febuxostat and 2.6 ± 1.7 mcg/mL at a dose of 80 mg febuxostat. A high-fat meal decreased Cmax by 49% and AUC by 18%, but there were no clinically significant changes in the ability of febuxostat to decrease serum uric acid concentrations.
Route of Elimination
Febuxostat is eliminated via both hepatic and renal pathways. Following oral administration of 80 mg radiolabeled febuxostat, approximately 49% of the dose was recovered in the urine. In urine, about 3% of the recovered dose accounted for unchanged febuxostat, 30% accounted for the acyl glucuronide metabolite, 13% accounted for oxidative metabolites and their conjugates, and 3% accounted for unidentified metabolites. Approximately 45% of the total dose was recovered in the feces, where 12% of the dose accounted for the unchanged parent drug. About 1% accounted for the acyl glucuronide metabolite, 25% accounted for oxidative metabolites and their conjugates, and 7% accounted for unidentified metabolites.
Volume of Distribution
The apparent steady-state volume of distribution (Vss/F) of febuxostat ranges from 29 to 75 L, indicating a low to medium volume of distribution.
Clearance
Following oral administration of single doses of 10 to 240 mg, the mean apparent total clearance ranged from 10 to 12 L/h.

8.6 Metabolism / Metabolites

Febuxostat is metabolized in the liver by UDP-glucuronosyltransferase (UGT) and Cytochrome P450 (CYP) enzymes, with the relative contribution of each enzyme isoform in the metabolism of febuxostat not fully elucidated. UGT1A1, UGT1A3, UGT1A9, and UGT2B7 mediate conjugation of febuxostat, which approximately accounts for 22–44% of the metabolism of the total dose administered, to produce the acyl-glucuronide metabolite. CYP1A2, CYP2C8, CYP2C9, and non-P450 enzymes are responsible for the oxidation reaction, which accounts for 2-8% of the metabolism of the dose. Oxidation reaction produces 67M-1, 67M-2, and 67M-4, which are pharmacologically active metabolites. 67M-1, 67M-2, and 67M-4 can further undergo glucuronidation and sulfation. Hydroxy metabolites are present in human plasma at much lower concentrations than the parent drug.

8.7 Biological Half-Life

The apparent mean terminal elimination half-life of approximately 5 to 8 hours.

8.8 Mechanism of Action

Gout is a form of acute arthritis that is characterized by the accumulation of crystals of monosodium urate and urate crystals in or around a joint, leading to inflammation and persistent urate crystal deposition in bones, joints, tissues, and other organs that may exacerbate over time. Hyperuricemia is closely related to gout, whereby it may exist for many years before the first clinical attack of gout; thus, aberrated serum uric acid levels and hyperuricemia are believed to be the biochemical aberration involved in the pathogenesis of gout. Xanthine oxidoreductase (XOR) can act as a xanthine oxidase or xanthine dehydrogenase. In humans, it is a critical enzyme for uric acid production as it catalyzes the oxidation reaction steps from hypoxanthine to xanthine and from xanthine to uric acid in the pathway of purine metabolism. Febuxostat potently inhibits XOR, blocking both its oxidase and dehydrogenase activities. With high affinity, febuxostat binds to XOR in a molecular channel leading to the molybdenum-pterin active site, where [allopurinol] demonstrates relatively weak competitive inhibition. XOR is mainly found in the dehydrogenase form under normal physiological conditions; however, in inflammatory conditions, XOR can be converted into the xanthine oxidase form, which catalyzes reactions that produce reactive oxygen species (ROS), such as peroxynitrite. ROS contribute to vascular inflammation and alterations in vascular function. As febuxostat can inhibit both forms of XOR, it can inhibit ROS formation, oxidative stress, and inflammation. In a rat model, febuxostat suppressed renal ischemia-reperfusion injury by attenuating oxidative stress.

9 Use and Manufacturing

9.1 Uses

9.1.1 Use Classification

Human drugs -> Antigout preparations -> Human pharmacotherapeutic group -> EMA Drug Category
Human Drugs -> EU pediatric investigation plans
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

Note
Pictograms displayed are for 94.1% (16 of 17) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 5.9% (1 of 17) of reports.
Pictogram(s)
Irritant
Health Hazard
Signal
Warning
GHS Hazard Statements

H302 (88.2%): Harmful if swallowed [Warning Acute toxicity, oral]

H362 (11.8%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]

H373 (11.8%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

H413 (17.6%): May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]

Precautionary Statement Codes

P203, P260, P263, P264, P270, P273, P301+P317, P318, P319, P330, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 17 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 1 of 17 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 6 notifications provided by 16 of 17 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

10.1.2 Hazard Classes and Categories

Acute Tox. 4 (88.2%)

Lact. (11.8%)

STOT RE 2 (11.8%)

Aquatic Chronic 4 (17.6%)

11 Toxicity

11.1 Toxicological Information

11.1.1 Hepatotoxicity

Liver test abnormalities have been reported to occur in 2% to 13% (average ~3.5%) of patients receiving febuxostat, but the levels are generally mild-to-moderate and self-limited. The height, nature and timing of these abnormalities have not been described. However, liver test elevations were the major reason for febuxostat discontinuation for adverse events (~2%) in clinical trials, despite the fact that no cases of jaundice or acute hepatitis were reported. Since its approval and more wide-scale use, there have been several individual case reports of liver injury attributed to febuxostat. Most cases have been marked by serum aminotransferase elevations without jaundice arising within days of starting febuxostat, including enzyme elevations in the setting of DRESS syndrome. At least one instance of a mixed-cholestatic hepatitis without immunoallergic features, arising after several months of treatment has been described. The product label for febuxostat lists hepatic steatosis, hepatitis and hepatomegaly as potential side effects. Furthermore, several cases of acute liver failure during febuxostat therapy have been reported to pharmacovigilance databases. Another unrelated, nonpurine xanthine oxidase inhibitor (benzbromarone) was not approved for use in the United States because of its potential for hepatic toxicity.

Likelihood score: C (probable rare cause of clinically apparent liver injury).

11.1.2 Drug Induced Liver Injury

Compound
febuxostat
DILI Annotation
Most-DILI-Concern
Severity Grade
8
Label Section
Warnings and precautions
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

11.1.3 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

No information is available on the use of febuxostat during breastfeeding. Because febuxostat is more than 99% bound to plasma proteins, the amount in milk is likely to be low. Furthermore, oral bioavailability is only about 50%, so the amount an infant receives systemically is expected to be very small. If febuxostat is required by the mother, it is not a reason to discontinue breastfeeding; however, until more data become available, an alternate drug may be preferred.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

11.1.4 Protein Binding

Febuxostat is approximately 99.2% bound to plasma proteins, primarily to albumin. Plasma protein binding is constant over the concentration range achieved with 40 mg and 80 mg doses.

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Springer Nature References

13.4 Thieme References

13.5 Chemical Co-Occurrences in Literature

13.6 Chemical-Gene Co-Occurrences in Literature

13.7 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 FDA Orange Book Patents

14.4 Chemical Co-Occurrences in Patents

14.5 Chemical-Disease Co-Occurrences in Patents

14.6 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Protein Bound 3D Structures

15.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

15.2 Chemical-Target Interactions

15.3 Drug-Drug Interactions

15.4 Drug-Food Interactions

Take with or without food. A high fat meal decreases Cmax and AUC in a clinically insignificant way.

16 Biological Test Results

16.1 BioAssay Results

17 Classification

17.1 MeSH Tree

17.2 NCI Thesaurus Tree

17.3 ChEBI Ontology

17.4 KEGG: Drug

17.5 KEGG: USP

17.6 KEGG: ATC

17.7 KEGG: Target-based Classification of Drugs

17.8 KEGG: Drug Groups

17.9 WHO ATC Classification System

17.10 FDA Pharm Classes

17.11 ChemIDplus

17.12 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

17.13 ChEMBL Target Tree

17.14 UN GHS Classification

17.15 NORMAN Suspect List Exchange Classification

17.16 CCSBase Classification

17.17 EPA DSSTox Classification

17.18 FDA Drug Type and Pharmacologic Classification

17.19 MolGenie Organic Chemistry Ontology

18 Information Sources

  1. BindingDB
    LICENSE
    All data curated by BindingDB staff are provided under the Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by/3.0/us/).
    https://www.bindingdb.org/rwd/bind/info.jsp
    2-(3-CYANO-4-ISOBUTOXY-PHENYL)-4-METHYL-5-THIAZOLE-CARBOXYLIC ACID
    https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50320491
  2. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  3. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  4. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  5. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  6. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  7. Therapeutic Target Database (TTD)
  8. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  9. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  10. DTP/NCI
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  11. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  12. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    2-[3-cyano-4-(2-methylpropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid (EC: 682-158-6)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/212292
  13. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  14. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  15. ChEBI
  16. FDA Pharm Classes
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  17. LiverTox
  18. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  19. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  20. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  21. Crystallography Open Database (COD)
    LICENSE
    All data in the COD and the database itself are dedicated to the public domain and licensed under the CC0 License. Users of the data should acknowledge the original authors of the structural data.
    https://creativecommons.org/publicdomain/zero/1.0/
  22. The Cambridge Structural Database
  23. DailyMed
  24. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  25. European Medicines Agency (EMA)
    LICENSE
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    https://www.ema.europa.eu/en/about-us/legal-notice
  26. Drugs and Lactation Database (LactMed)
  27. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  28. EU Clinical Trials Register
  29. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  30. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    FEBUXOSTAT
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  31. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  32. FDA Medication Guides
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  33. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  34. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  35. Japan Chemical Substance Dictionary (Nikkaji)
  36. Japan Pharmaceuticals and Medical Devices Agency (PMDA)
  37. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  38. MassBank Europe
  39. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  40. Metabolomics Workbench
  41. NIPH Clinical Trials Search of Japan
  42. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  43. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  44. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  45. Protein Data Bank in Europe (PDBe)
  46. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  47. SpectraBase
  48. Springer Nature
  49. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  50. Wikidata
  51. Wikipedia
  52. Medical Subject Headings (MeSH)
    LICENSE
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    https://www.nlm.nih.gov/copyright.html
  53. PubChem
  54. GHS Classification (UNECE)
  55. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  56. PATENTSCOPE (WIPO)
  57. NCBI
CONTENTS